The structure of the peptide hormone glucagon is being studied by physical and chemical techniques for the purpose of relating its structure to its functions. A number of side-chain modifications and cleavage products have been prepared, isolated and chemically characterized to define the role of specific amino acid side chains for binding to hormone receptors and to antiglucagon antibodies. Amino-terminal modifications will follow the same strategy except that binding will be less affected than adenyl cyclase activation. Such studies are essential for the efficient design of analogues of potential therapeutic usefulness.